Action of almitrine on the pulmonary vasculature in ferrets and rats

The action of almitrine on pulmonary vessels was studied under constant ventilation during normoxia and hypoxia. We used ferrets, in which one lobe of lung was perfused with venous blood at constant flow rate in vivo and isolated lungs perfused with blood at constant flow in both ferrets and normal and chronically hypoxic (three weeks in 10% O2) rats. Almitrine caused constriction of the relaxed vessels of normoxic lung. During hypoxic pulmonary vasoconstriction, when pulmonary artery pressure (Ppa) was raised, almitrine had a dual action; it caused further constriction followed by dilatation over a wide dose range (0.7-118 micrograms X kg-1 in ferrets). Similar effects were seen in normal and chronically hypoxic rats; the latter have narrowed muscularized arterioles like patients with chronic obstructive airways disease. Almitrine caused a larger rise in Ppa in normoxic than hypoxic rat lungs (7.9 instead of 1.7 mmHg; p less than 0.001) and dilatation followed constriction in the latter. Verapamil reduced both the constrictor action of almitrine and hypoxic vasoconstriction and there was a strong correlation between the effect of the two stimuli before and after verapamil (r = 0.9). Attempts to identify a substance which might cause the dilator action of almitrine were unsuccessful.